Comparative transcriptomic response of bank vole kidney and respiratory epithelial cells to distinct orthohantaviruses

Orthohantaviruses are rodent-borne viruses distributed worldwide that can cause diseases of varying severity in humans following occasional aerosol transmission. While infections remain asymptomatic in their natural small-mammal reservoirs, hantaviral pathogenesis in humans is associated with an exacerbated immune response. The increasing number of outbreaks in endemic regions caused by the modification of rodent habitats due to human activities and the risks of reassortments in areas where multiple orthohantaviruses co-circulate with their animal reservoirs, are of public health concern. These challenges highlight the need to better understand how these viruses interact with host cells to spread within and between organisms, and how antiviral responses are regulated, particularly in their natural hosts. We previously showed that cellular susceptibility to orthohantaviruses depends on both cell type and virus species and correlates with cellular restrictions acting at different stages of the viral cycle. Here, we performed a comparative RNA-sequencing study and transcriptomic analysis of the cellular responses induced by three different orthohantaviruses in kidneys and respiratory tract cells derived from bank voles, the natural host of an orthohantavirus pathogenic to humans. Transcriptomic analyses revealed common as well as virus- and tissue-specific regulatory pathways that may underlie distinct infection outcomes. It highlighted the complexity of viral interactions with bank vole at a cellular level, including innate immune responses and antiviral signaling pathways.